Respiratory hemoproteins such as myoglobin, hemoglobin, and cytochromes from various biological sources are modified by chemical exchange of the prosthetic groups and selective modifications of the apoprotein moieties. Effects of such modifications on biochemical functions of the hemoproteins, the electronic state of their prosthetic groups are characterized using various physical and chemical techniques, which include automatic oxygenation measurements, optical spectroscopy, electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR) spectroscopy, Mossbauer spectroscopy, and fluorescence spectroscopy, in order to establish the correlation between molecular structure and biochemical function of these hemoproteins. These modification techniques are further applied to the studies of the mode of interaction of hemoproteins with other hemoproteins and with natural and artifical membranes, and the mechanism of subunit cooperativity and the mode of action of allosteric effectors such as 2,3-diphosphoglycerate and inositol hexaphosphate in oligomeric hemoproteins. Physiological significance of functions of these hemoproteins in isolated states and those in organized systems will be evaluated. On the basis of knowledge and techniques acquired in these basic researches, the chemical syntheses of artifical hemoproteins, particularly artifical hemoglobin which possesses more favorable functional properties for biomedical applications than the natural counterpart will be attempted. BIBLIOGRAPHIC REFERENCES: Imai, K., and Yonetani, T. (1975) J. Biol. Chem., 250, 2224-2231, pH-dependence of the Adair constants of human hemoglobin: Non-uniform contribution of successive oxygen binding to the alkaline Bohr effect. Imai, K., and Yonetani, T. (1975) J. Biol. Chem., 250, 7083-7098; Thermodynamic studies of oxygen equilibrium of hemoglobin: Non-uniform heat and entropy changes for the individual oxygenation steps and entropy-enthalpy compensation.